http://www.newscientist.com/article.ns?id=dn8347
GM Pea Causes Allergic Damage in Mice
11:18 21 November 2005
NewScientist.com news service
Emma Young, Sydney
A decade-long project to develop genetically modified peas with
built-in pest-resistance has been abandoned after tests showed they
caused allergic lung damage in mice.
The researchers at Australias national research organisation, CSIRO
took the gene for a protein capable of killing pea weevil pests from
the common bean and transferred it into the pea. When extracted from
the bean, this protein does not cause an allergic reaction in mice or
people.
But the team found that when the protein is expressed in the pea, its
structure is subtly different to the original in the bean. They think
this structural change could be to blame for the unexpected immune
effects seen in mice.
The work underlines the need to evaluate new GM crops on a
case-by-case basis, says Paul Foster of the Australian National
University in Canberra, who led the immunological work. He also calls
for improvements in screening requirements for genetically engineered
plants, to ensure comprehensive tests are carried out.
Jeremy Tager, Greenpeace Australias campaigner on genetic
engineering, agrees. These results indicate the potential for
unpredicted and unintended changes in the structure of transferred
proteins. And Im not aware of any country that requires feeding
studies as part of its approval process.
Completely Resistant
Field peas (Pisum sativum) are susceptible to the pea weevil Bruchus
pisorum, which lays its eggs on the pea pods. The weevil frequently
devastates crops not only in Australia but across the developing world.
The common bean (Phaseolus vulgaris) contains alpha-amylase
inhibitor-1, a protein that inhibits the activity of alpha-amylase, an
enzyme that is used by pea weevils to help them digest starch.
CSIRO Plant Industry researchers hoped the developing weevils would
starve after eating the protein, before they could cause any real
damage to the crop. Trials showed that the GM peas were almost
completely resistant to the pea weevils.
Hypersensitive Skin
Foster and his team then used mice to investigate whether eating the GM
peas might have any undesirable immune impact. Generally, digested
proteins do not create a specific immune system response.
But researchers found that mice that ate transgenic pea seed did
develop antibodies specific to the protein. Some of these mice were
later exposed to the purified protein, either through injection into
the blood, or by putting the protein into their airways.
This approach is a standard "multiple immune challenge" procedure and
is designed to determine if the immune system is tolerant to a protein.
The injected mice showed a hypersensitive skin response, while the
airway-exposed mice developed airway inflammation and mild lung damage.
The effect was the same whether the protein was taken from raw or
cooked peas so whether the protein was active or denatured. To my
knowledge, this is the first description of inducing experimental
inflammation in mice with a GM food, Foster says. In the early 1990s,
researchers engineered a more nutritious strain of soya bean by adding
a gene taken from brazil nuts. But the project ended when it was
discovered that the hybrid was likely to trigger a major attack in
people with brazil nut allergies.
Human Consumption
Further investigations by Fosters team revealed slight differences in
the molecular structure of the protein when it was expressed in the
bean and in the pea. They think this was caused by differences in the
way the two plants produce proteins particularly in a step called
glycosylation, which involves adding saccharides to the protein.
When expressed in the pea, the protein was glycosylated at different
points thats the only structural change weve been able to identify
so far, says Foster.
He adds that slight differences in protein synthesis might also occur
in other plants with other genes, meaning each new GM food should be
very carefully evaluated for potential health effects. If a GM plant
is to go up for human consumption, there should be a detailed
descriptive list of how one should go about analysing that plant, he
says.
Tager agrees. It is rare for an investigation of the potential health
effects of a GM product to be published in a peer-reviewed journal, he
adds. If it had been a private company doing this, it might never have
seen the light of day, he says.